Alan H. Bryce, MD

Alan H. Bryce, MD, assistant professor of medicine and medical director of the Genomic Oncology Clinic, Mayo Clinic, discusses the accelerated approval of rucaparib (Rubraca) for the treatment of adult patients with 

 mutation (germline and/or somatic)—associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

The accelerated approval is based on findings from the ongoing phase 2 TRITON2 trial (NCT02952534), in which the PARP inhibitor demonstrated a 44% confirmed objective response rate (ORR) in 62 evaluable patients with 

The results of the TRITON2 trial confirm historical data showing the efficacy of PARP inhibitors in 

-mutant prostate cancer, says Bryce. The regulatory decision marks the first approval for a biomarker-driven targeted therapy in prostate cancer, says Bryce. With this approval, patients with 

-mutant mCRPC now have access to an extremely effective and attractive treatment option, concludes Bryce.

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Alan H. Bryce, MD, discusses the accelerated approval of rucaparib (Rubraca) for the treatment of adult patients with BRCA mutation (germline and/or somatic)–associated metastatic castration-resistant prostate cancer (mCRPC) who have been treated with androgen receptor–directed therapy and a taxane-based chemotherapy.

Dr. Bryce on the FDA Approval of Rucaparib in BRCA-Mutant mCRPC

Alan H. Bryce, MD, assistant professor of medicine and medical director of the Genomic Oncology Clinic, Mayo Clinic, discusses ongoing research regarding 

-altered prostate cancer accounts for 5% to 10% of all prostate cancers, says Bryce. Patients with a 

 mutation have a poor response to traditional antiandrogen agents such as abiraterone acetate (Zytiga) and enzalutamide (Xtandi), and PARP inhibitors. However, these patients appear to respond well to immunotherapy.

CDK12 appears to regulate chromosomal stability, says Bryce. As such, a 

 mutation can lead to large tandem duplications and chromosomal rearrangements, which increases neoantigen production.

In a retrospective, multicenter analysis of 58 men with monoallelic 

 alterations, 8 patients with metastatic castration-resistant prostate cancer had been treated with a PD-1 inhibitor. Among these patients, 38% had a prostate specific antigen

) response, explains Bryce. Additionally, none of the 11 patients treated with a PARP inhibitor had a PSA

With further research, CDK12 could become a biomarker of response to checkpoint inhibitors in prostate cancer, concludes Bryce.

Alan H. Bryce, MD, discusses ongoing research regarding CDK12 alterations in prostate cancer.

Dr. Bryce on Ongoing Research Regarding CDK12 Alterations in Prostate Cancer

Alan H. Bryce, MD, assistant professor of medicine and medical director of the Genomic Oncology Clinic, Mayo Clinic, discusses ongoing research in prostate cancer.

The ongoing phase III AFT19 trial is evaluating apalutamide (Erleada) in patients with biochemically relapsed disease. In the 3-arm study, patients will be randomized to receive either androgen deprivation therapy (ADT) alone, ADT plus apalutamide, or ADT, apalutamide, and abiraterone acetate (Zytiga).

Similar to the phase III CHAARTED and STAMPEDE studies, AFT19 is trying to take effective agents and bring them into earlier-line settings, which could potentially translate to significant improvements in overall survival, explains Bryce.

In addition, more studies taking approved agents in metastatic castration-resistant disease and moving them into the hormone-sensitive and nonmetastatic setting are expected, concludes Bryce.

Dr. Bryce on Ongoing Research in Prostate Cancer

Alan H. Bryce, MD, assistant professor of medicine, Mayo Clinic, discusses the use of next-generation radiopharmaceuticals in prostate cancer.

A study with lutetium-177, which is attached to prostate-specific membrane antigen (PSMA), has recently completed accrual, says Bryce. In prostate cancer, PSMA receptors are overexpressed on the surface of cancer cells. As such, when lutetium-177 is combined with PSMA, the radioactive isotope is easily delivered to malignant cells. Unlike radium-223, PSMA-targeting is delivered equally in bone, soft tissue, and other locations of metastasis within the body, explains Bryce. Once the PSMA delivers the radiation to the prostate cancer cell, the lutetium radiation decays around the cancer cell.

The treatment strategy was originally developed in Germany and then was tested in Australia, says Bryce. Encouraging signals of activity were reported in preliminary single-arm studies. As such, Bryce is hopeful that the phase III study could show similar findings.

Author | Alan H. Bryce, MD

Articles

Dr. Bryce on the FDA Approval of Rucaparib in BRCA-Mutant mCRPC

Dr. Bryce on Ongoing Research Regarding CDK12 Alterations in Prostate Cancer

Dr. Bryce on Ongoing Research in Prostate Cancer

Dr. Bryce on Next-Generation Radiopharmaceuticals in Prostate Cancer